In hyperthermia treatment of cancer, tumors are elevated to cytotoxic temperatures (41 - 45oC) in order to aid in their control. Noninvasive temperature imaging would enhance the ability to uniformly heat tumors at therapeutic levels. Our long-term goal is to produce 3-dimensional (3D) temperature maps in soft tissue, noninvasively, conveniently, and at low cost, with 0.5oC accuracy and 1cm3 resolution. Ultrasound is an attractive modality for this purpose. Changes in speed of sound, attenuation, and the location of echoes have been explored by others, but as yet not reduced to clinical practice. Here we plan to investigate changes in ultrasonic backscattered energy (CBE) with temperature to provide a foundation for judging the accuracy and spatial resolution of this approach. Previously, we predicted monotonic changes in CBE for certain sub wavelength scatterers. We have measured CBE values similar to our predictions in images of tissue that were compensated for apparent axial and lateral motion in the images. To extend this preliminary work performed with R21 funding we plan the following: 1) to validate our model for the temperature-dependent change in backscattered ultrasonic energy (CBE) from individual scatterers using histological studies, and to extend it by developing an efficient computational framework for estimating temperature-dependent CBE from simulated images of collections of scatterers; 2) to generate experimental data in order to characterize CBE as a function of temperature in 3D from ex vivo specimens and in 2D from in vivo preparations while identifying CBE effects that are dependent on the imaging system; and 3) to develop motion tracking algorithms to compensate for real and/or apparent motion that obscures the temperature dependence of CBE then calibrate CBE in motion-compensated images for temperature estimation. If changes in backscattered energy can be used to estimate temperature accurately and reliably, the benefits could be important for hyperthermia, other thermal therapies, and ultrasonic imaging in general. In vivo success of CBE temperature estimation in animal preparations through the proposed studies will serve as the foundation for the eventual generation of 3D temperature maps in soft tissue in a noninvasive, convenient, and low-cost way in clinical hyperthermia.